1. Field of the Invention
This invention generally relates to coatings or implantable devices, such as stents or coatings on a stent, formed of a material that contains amorphous poly(D,L-lactide) (PDLLA) with a crystallinity of about or lower than 10%.
2. Description of the Background
Although stents work well mechanically, the chronic issues of restenosis and, to a lesser extent, stent thrombosis remain. Pharmacological therapy in the form of a drug-delivery stent appears a feasible means to tackle these biologically derived issues. Polymeric coatings placed onto the stent serve to act both as the drug reservoir, and to control the release of the drug. One of the commercially available polymer coated products is stents manufactured by Boston Scientific. For example, U.S. Pat. Nos. 5,869,127; 6,099,563; 6,179,817; and 6,197,051, assigned to Boston Scientific Corporation, describe various compositions for coating medical devices. These compositions provide to stents described therein an enhanced biocompatibility and may optionally include a bioactive agent. U.S. Pat. No. 6,231,590 to Scimed Life Systems, Inc., describes a coating composition, which includes a bioactive agent, a collagenous material, or a collagenous coating optionally containing or coated with other bioactive agents.
A current paradigm in biomaterials is the control of protein adsorption on the implant surface. Uncontrolled protein adsorption, leading to mixed layer of partially denatured proteins, is a hallmark of current biomaterials when implanted. Such a surface presents different cell binding sites from adsorbed plasma proteins such as fibrogen and immunogloblulin G. Platelets and inflammatory cells such as monocyte/macrophages and neutrophils adhere to these surfaces. Unfavorable events can be controlled by the use of non-fouling surfaces. These are materials, which absorb little or no protein, primarily due to their hydrophilic surface properties.
Another limitation of current drug-delivery stents stems from the fact that the stent is a foreign body. Use of drug-delivery stents has proved successful by use of controlled release of anti-proliferative or anti-inflammatory drugs to control restenosis. However, drug-delivery stents still have a small, but measurable, incidence of sub-acute thrombosis. Moreover, drug-delivery stents have not driven restenosis to zero levels, especially in more challenging patient subsets such as diabetics or patients with small vessels, and/or long, diffuse lesions. A biomaterials-based strategy for further improving the outcome of drug-delivery stents is by the use of biobeneficial materials or surfaces in stent coatings. A biobeneficial material is one which enhances the biocompatibility of a device by being non-fouling, hemocompatible, actively non-thrombogenic, or anti-inflammatory, all without depending on the release of a pharmaceutically active agent.
Poly(lactic acid) (PLA) is a bioabsorbable material with a long history of use. One of the negative aspects of using bioabsorbable material is late term inflammatory reactions. One of the reasons causing late term inflammatory reactions is a burst release of acidic degradation products at a late time point. Another cause is the release of polymer crystallites at a late time point once the amorphous polymer phase has degraded. It has been well documented that polymerization of D,L-lactic acid, and during degradation of the resulting polymers, can lead to the formation of stereocomplexes of PLA polymers. These stereocomplexes are the result of co-crystallization of enatiomerically pure poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) polymers or polymeric blocks (see, for example, Ikada, Y., et al., Macromolecules 20:904-06 (1987)). Studies have shown that these stereocomplexes have crystalline structures (see, for example, Okihara, T., et al., J. Macromol. Sci. Phys. B30(1/1):119-140 (1991); Tsuji, H., et al., Macromolecules 24:5651-6 (1991)). Accordingly, PLA formed by polymerization of D,L-lactic acids which allows for the formation of homologous sequences of L-lactic and/or D-lactic acid may cause late term inflammatory reactions.
The present invention addresses such problems by providing a polymeric material for coating implantable devices.